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Existing systemic treatments for New World cutaneous leishmaniasis (CL) caused by Leishmania (vianna) braziliensis are unsatisfactory. Liposomal amphotericin B has been used extensively for the treatment of visceral leishmaniasis, but in few cases of CL, and an appropriate regimen for CL has not been described. We successfully treated a patient with multiple L. braziliensis CL lesions acquired in Belize. Liposomal amphotericin B (AmBisome) was given to our patient as an inpatient for seven daily doses of 3 mg kg(-1) day(-1) and then as an outpatient at 3 mg kg(-1) twice weekly for a further three weeks, a total of 40 mg kg(-1). Liposomal amphotericin offers a well-tolerated alternative to pentavalent antimony or amphotericin B deoxycholate for the systemic treatment of New World CL.

We used liposomal amphotericin B as first-choice treatment of visceral leishmaniasis in 106 immunocompetent children who acquired the infection in a temperate region of southern Europe (Italy) where Leishmania infantum visceral leishmaniasis is endemic. The aim of the study was to identify the minimum total dose of liposomal amphotericin B needed to cure the infection in children and reduce the period of hospitalization. We conclude that the optimal regimen in immunocompetent children with L. infantum visceral leishmaniasis to be a total dose of 18 mg/kg of liposomal amphotericin B (3 mg/kg per day for 5 days, followed by 3 mg/kg administered as an outpatient regimen on day 10).

We evaluated liposomal amphotericin B (AmBisome; Vestar, San Dimas, CA) administered to 88 immunocompetent patients (56 children) with visceral leishmaniasis (VL) caused by Leishmania infantum. Thirteen patients received 4 mg/kg on days 1-5 and 10 (total dose, 24 mg/kg), and all were cured; 42 received 3 mg/kg on days 1-5 and 10 (18 mg/kg), and 41 were cured; 32 received 3 mg/kg on days 1-4 and 10 (15 mg/kg), and 29 were cured (amastigotes were not cleared from 1 child, and 2 relapsed). One adult was cured with a total dose of 12mg/kg. The four children who were not cured received 3 mg/kg for 10 days; none had further relapses. There were no significant adverse events. For VL due to L. infantum, we recommended a total dose of AmBisome of > or = 20 mg/kg, given in > or = 5 doses of 3-4 mg/kg over > or = 10 days.

The rapidity and efficacy of a short course of liposomal amphotericin B was evaluated in 29 children affected by visceral leishmaniasis (Leishmania infantum). Their overall health status was assessed using the prognostic inflammatory and nutritional index (PINI), and their haematological status by the reticulocyte count and haemoglobin blood levels. All these quantities were measured on day 0, and 3 and 10 d after starting therapy. A significant decrease of inflammatory signs, associated with an improved reticulocyte count, was recorded after 3 d of therapy. A significant increase of haemoglobin levels was also observed 10 d after the start of treatment. The early reduction of inflammatory signs and the improvement of bone marrow function in most patients confirmed the validity of amphotericin B therapy. The PINI score is helpful in assessing the severity of visceral leishmaniasis and the follow-up of its treatment.

Visceral leishmaniasis (VL) in patients coinfected with human immunodeficiency virus (HIV) is often atypical, and characteristically relapses after treatment. We treated 10 HIV infected patients (9 men) with parasitologically confirmed VL with liposomal amphotericin B ("AmBisome': L-AMB) at a dose of 4 mg/kg/day on days 1, 2, 3, 4, 5, 10, 17, 24, 31, and 38. Patients were hospitalized for the first 5 days, and were monitored during, and 1 week and 1, 3 and 6 months after, L-AMB therapy. There were no serious adverse events, and L-AMB was well tolerated. 9/10 patients completed therapy, one patient defaulted at day 24. Clinical improvement was seen in all nine patients and the bone marrow aspirate was cleared of visible/culturable parasites in 8/9 patients. During follow-up, one patient defaulted. The seven remaining patients relapsed at 2, 3, 3, 5, 5, 6 and 7 months. Re-treatment with a variety of antileishmanial drugs was unsatisfactory. The time from first diagnosis of VL to death in six patients was 5-40 months (mean 18.8 months). Only one patient remained alive 26 months after treatment. L-AMB is safe and provides a good initial clinical response. Intermittent dosing enables a short period of hospitalization. However, relapse is probably inevitable.

Thirteen dogs naturally infected with Leishmania infantum showing viscero-cutaneous signs of disease were treated with different dosages of liposomal amphotericin B (AmBisome). The animals were followed clinically and parasitologically over a period of eight months. Dogs which received three to five administrations of AmBisome 3-3.3 mg/kg showed rapid clinical improvement, with regression of lymphadenomegaly and splenomegaly, and cure of skin lesions. The clinical response was similar to that obtained with 14-21 doses of conventional antileishmanial drugs. However, follow-up lymph node aspirates remained positive for Leishmania in all dogs except one, which was treated with the total dose of AmBisome 15 mg/kg. The failure in parasitological cure may be due to inadequate drug targeting to parasitized cells, or to T-cell immune depression characteristic of patent cases of canine leishmaniasis, or to both.

Thirty-one patients with visceral leishmaniasis (VL) caused by Leishmania infantum received liposomal amphotericin B (AmBisome) in a multi-centre study. Ten immunocompetent patients (six children) received 1-1.38 mg/kg/day for 21 days, and ten (nine children) received 3 mg/kg/day for 10 days. All were cured without significant adverse events and without relapse during 12-24 months of follow-up. Eleven immunocompromised adults, including seven co-infected with HIV (four with AIDS) received 100 mg (1.38-1.85 mg/kg) daily for 21 days. All were initially considered cured, but eight relapsed clinically and parasitologically at 3-22 months. Liposomal amphotericin B is a new, safe and effective drug for the treatment of VL.

Preliminary observations have shown that AmBisome, a liposomal formulation of amphotericin B (Vestar Inc.), is effective and non-toxic in animal and human visceral leishmaniasis. The activity of multiple doses of this drug on Leishmania infantum, in BALB/c mice was investigated, and amphotericin B concentration in liver and spleen was determined. Groups of infected mice were treated intravenously with 3, 5, or 7 doses of AmBisome (3 mg/kg) over 3, 10 and 25 days, respectively. The antileishmanial activity of the drug was compared with that of meglumine antimoniate (28 mg Sbv/kg per day over 21 days). Three consecutive daily doses of AmBisome were sufficient to clear all parasites from the liver of mice, while antimony did so only after 21 doses. Twenty-four-48 h after their last dose all the AmBisome-treated mice showed very high amphotericin B concentrations in liver (61.2-76.2 micrograms/g) and spleen (39.8-72.1 micrograms/g) with no overt signs of toxicity. Mice that received 2 or 4 doses at intervals of 5 to 8 days, maintained drug levels as high as those detected after 3 consecutive doses over 11 and 26 days, respectively. This should enable visceral leishmaniasis treatment on an intermittent or outpatient basis, thereby reducing overall treatment costs.

A case of visceral leishmaniasis unresponsive to several course of treatment with standard drugs, was successfully cured by a 21 day course (50 mg/day) of liposomal amphotericin B (AmBisome, Vestar Inc.). The efficacy of the AmBisome formulation is supported by experimental studies on Leishmania donovani infected BALB/c mice where ED50 values of AmBisome and conventional amphotericin B were 0.15-0.25 and 0.95-4.9 mg/kg, respectively. A lack of toxicity of the AmBisome formulation was noted in both studies.

The treatment of visceral leishmaniasis (VL) may be complicated by drug toxicity or intolerance, and by drug resistance. Amphotericin B (AmB) is effective, but its use is limited by toxicity: renal impairment, anaemia, fever, malaise, and hypokalaemia are common. Liposomes have been proposed as an effective way to target drugs at macrophages, which are the cells infected in visceral leishmaniasis. In animals AmB incorporated into liposomes is highly effective against experimental leishmaniasis, with low toxicity. This report is of the successful treatment of a patient with multiply drug-resistant visceral leishmaniasis with a commercially prepared formulation of liposomal amphotericin B (L-AmB) ('AmBisome', Vestar, San Dimas, California, USA). We also report, for comparison, a patient treated with conventional AmB, and preliminary studies in mice comparing the two agents.